NCT03383211

Immune Response to BCG Vaccination in Neonates Born to HIV and LTBI Infected and Non-infected Mothers

Transcriptomic Profile of the Immune Response to BCG Vaccination in Neonates Born to HIV and LTBI Infected and Non-infected Mothers

• Status: Completed
• Phase: —
• Study type: Observational
• Enrollment: 125 (actual)
• Sponsor: George Washington University · Academic / Other
• Sex: Female
• Age: 18 Years – 45 Years
• Healthy volunteers: Accepted

Summary

Maternal infections affect the basal immune status of neonates. One of the possible mechanism is the fetomaternal microchimerism, in which some cells and active substances are exchanged bi-directionally between maternal and fetal circulation through placenta. Even in the absence of a direct (vertical) transmission of pathogens to fetuses, certain infections make the neonates more prone to allergies and some adverse events of early vaccinations. We postulate that the basal immune status of neonates born to HIV and LTBI infected mothers is primed by gestational exposure to immunological active molecules, which could results in an altered response to early BCG vaccination. Transcripts expression identified by RNA sequencing are compared between sets of mother-child and their respective umbilical cord blood, and between groups of infected and non-infected pairs.

Detailed description

The study is comparing the transcriptomic profiles of maternal peripheral blood with those of the corresponding umbilical cord blood and neonatal peripheral blood pre- and post-BCG vaccination. For RNA sequencing, the samples are collected in Tempus RNA Blood tubes at 5 time-points (TP): maternal peripheral blood at the time of initial diagnosis with HIV (first OBGYN consultation @ 12-16 weeks of pregnancy - TP1); repeated HIV test in 3rd trimester of pregnancy (34-36 weeks- TP2); umbilical cord blood (after delivery and ligation- TP3); neonates (24 hours after birth and after HBV vaccination, prior to BCG vaccination- TP4); and neonates (7 days after BCG vaccination- TP5). As an indicator of the inflammatory status, the peripheral blood samples collected at the same TP are stained for serological markers of inflammation, exhaustion, maturation and activation. An advanced bioinformatics analysis examines the immune-associated transcripts in RNAseq samples to assess the V(D)J recombination of T-cell and B-cell receptors along with immune-associated SNPs. The main goal of the study is to identify in umbilical cord blood the genomic biomarkers of the neonatal basal immune status for guiding an optimal BCG immunization protocol for such neonates and to avoid potential adverse events after vaccination.

Conditions

• HIV Infections
• Neonatal Infection
• LTBI - Latent Tuberculosis Infection
• Immune Tolerance

Interventions

Type	Name	Description
OTHER	RNAseq	Transcriptome profiling of peripheral blood using RNA sequencing technology

Timeline

• Start date: 2017-06-16
• Primary completion: 2020-09-01
• Completion: 2021-06-30
• First posted: 2017-12-26
• Last updated: 2021-10-20

Locations

2 sites across 1 country: Moldova